Safety and Efficacy Study of Idelalisib (GS-1101, CAL-101) in Patients With Previously Treated Low-grade Lymphoma
Study Details
Study Description
Brief Summary
The primary objectives of this study is to evaluate the safety and efficacy of idelalisib (GS-1101, CAL-101) in participants with previously treated indolent non-Hodgkin lymphoma (iNHL).
Eligible patients will initiate oral therapy with idelalisib at a starting dose of 150 mg twice per day. Treatment with idelalisib can continue in compliant participants for up to twelve 28-day cycles of idelalisib. Participants who appear to be benefiting from treatment at the completion of 12 cycles of treatment with idelalisib may be eligible for participation in a long-term safety extension study of idelalisib.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Idelalisib
|
Drug: Idelalisib
Tablet(s) administered orally twice daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Safety of Idelalisib [30 days post last study treatment (up to 12 months)]
The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).
- Clinical Response: Overall Response Rate [Up to twelve 28-day cycles (maximum of 12 months)]
Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. CR was defined as the disappearance of all evidence of disease. PR was defined the regression of measurable disease and no new sites.
Secondary Outcome Measures
- Flow Cytometric Measurement of Constitutive or Inducible Phosphorylation of Akt (at S473) and S6 Within Tumor B Cells [Up to twelve 28-day cycles (maximum of 12 months)]
- Flow Cytometric Measurement of Tumoral and Peripheral Blood T and NK Cells [Up to twelve 28-day cycles (maximum of 12 months)]
- Changes in Concentration of Peripheral Blood Chemokines and Cytokines [Up to twelve 28-day cycles (maximum of 12 months)]
- Changes in Liver Imaging as Assessed by Magnetic Resonance Imaging (MRI) and Gadoxetic Acid (GD-EOB-DTPA) Contrast [Up to twelve 28-day cycles (maximum of 12 months)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Previously treated relapsed or refractory B-cell iNHL
-
Provide written informed consent
Exclusion Criteria:
-
Pregnant or nursing
-
Active, serious infection requiring systemic therapy
-
Positive test for HIV antibodies
-
Active hepatitis B or C viral infection
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Stanford Cancer Center | Palo Alto | California | United States | 94304-5548 |
2 | Mount Sinai School of Medicine | New York | New York | United States | 10029 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 101-10
Study Results
Participant Flow
Recruitment Details | Participants were enrolled at 2 study sites in the United States. The first participant was screened on 22 February 2011. The last study visit occurred on 24 August 2015. |
---|---|
Pre-assignment Detail | 24 participants were screened. |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Period Title: Overall Study | |
STARTED | 18 |
COMPLETED | 5 |
NOT COMPLETED | 13 |
Baseline Characteristics
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Overall Participants | 18 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
58
(12.6)
|
Sex: Female, Male (Count of Participants) | |
Female |
8
44.4%
|
Male |
10
55.6%
|
Diagnosis (participants) [Number] | |
Follicular lymphoma |
10
55.6%
|
Marginal zone lymphoma |
3
16.7%
|
Small lymphocytic lymphoma |
4
22.2%
|
Missing |
1
5.6%
|
Outcome Measures
Title | Overall Safety of Idelalisib |
---|---|
Description | The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib). |
Time Frame | 30 days post last study treatment (up to 12 months) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) Analysis Set: all enrolled participants who received at least 1 dose of idelalisib. |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Measure Participants | 18 |
Any AE |
88.9
493.9%
|
Serious AE |
27.8
154.4%
|
Grade ≥ 3 AE |
55.6
308.9%
|
AE related to idelalisib |
83.3
462.8%
|
AE leading to permanent drug discontinuation |
27.8
154.4%
|
Title | Clinical Response: Overall Response Rate |
---|---|
Description | Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. CR was defined as the disappearance of all evidence of disease. PR was defined the regression of measurable disease and no new sites. |
Time Frame | Up to twelve 28-day cycles (maximum of 12 months) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Analysis Set |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Measure Participants | 18 |
Number (95% Confidence Interval) [percentage of participants] |
44.4
246.7%
|
Title | Flow Cytometric Measurement of Constitutive or Inducible Phosphorylation of Akt (at S473) and S6 Within Tumor B Cells |
---|---|
Description | |
Time Frame | Up to twelve 28-day cycles (maximum of 12 months) |
Outcome Measure Data
Analysis Population Description |
---|
Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead. |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Measure Participants | 0 |
Title | Flow Cytometric Measurement of Tumoral and Peripheral Blood T and NK Cells |
---|---|
Description | |
Time Frame | Up to twelve 28-day cycles (maximum of 12 months) |
Outcome Measure Data
Analysis Population Description |
---|
Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead. |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Measure Participants | 0 |
Title | Changes in Concentration of Peripheral Blood Chemokines and Cytokines |
---|---|
Description | |
Time Frame | Up to twelve 28-day cycles (maximum of 12 months) |
Outcome Measure Data
Analysis Population Description |
---|
Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead. |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Measure Participants | 0 |
Title | Changes in Liver Imaging as Assessed by Magnetic Resonance Imaging (MRI) and Gadoxetic Acid (GD-EOB-DTPA) Contrast |
---|---|
Description | |
Time Frame | Up to twelve 28-day cycles (maximum of 12 months) |
Outcome Measure Data
Analysis Population Description |
---|
Data are not available because the samples and analysis results (performed at the sites) could not be retrieved by Gilead. |
Arm/Group Title | Idelalisib |
---|---|
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles |
Measure Participants | 0 |
Adverse Events
Time Frame | 30 days post last study treatment (up to 12 months) | |
---|---|---|
Adverse Event Reporting Description | ITT Analysis Set | |
Arm/Group Title | Idelalisib | |
Arm/Group Description | Idelalisib 150 mg tablet(s) administered orally twice daily for a maximum of twelve 28-day cycles | |
All Cause Mortality |
||
Idelalisib | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Idelalisib | ||
Affected / at Risk (%) | # Events | |
Total | 5/18 (27.8%) | |
Cardiac disorders | ||
Atrial fibrillation | 1/18 (5.6%) | |
Gastrointestinal disorders | ||
Gastrointestinal haemorrhage | 1/18 (5.6%) | |
Infections and infestations | ||
Cellulitis | 1/18 (5.6%) | |
Sepsis | 1/18 (5.6%) | |
Investigations | ||
Alanine aminotransferase increased | 1/18 (5.6%) | |
Aspartate aminotransferase increased | 1/18 (5.6%) | |
Transaminases increased | 1/18 (5.6%) | |
Metabolism and nutrition disorders | ||
Tumour lysis syndrome | 2/18 (11.1%) | |
Renal and urinary disorders | ||
Renal failure | 2/18 (11.1%) | |
Respiratory, thoracic and mediastinal disorders | ||
Hypoxia | 1/18 (5.6%) | |
Pneumonitis | 1/18 (5.6%) | |
Pneumothorax | 1/18 (5.6%) | |
Other (Not Including Serious) Adverse Events |
||
Idelalisib | ||
Affected / at Risk (%) | # Events | |
Total | 15/18 (83.3%) | |
Blood and lymphatic system disorders | ||
Neutropenia | 3/18 (16.7%) | |
Thrombocytopenia | 2/18 (11.1%) | |
Cardiac disorders | ||
Atrial fibrillation | 1/18 (5.6%) | |
Atrial tachycardia | 1/18 (5.6%) | |
Palpitations | 1/18 (5.6%) | |
Ear and labyrinth disorders | ||
Vertigo | 2/18 (11.1%) | |
Eye disorders | ||
Blepharospasm | 1/18 (5.6%) | |
Chalazion | 1/18 (5.6%) | |
Conjunctival hyperaemia | 1/18 (5.6%) | |
Keratitis | 1/18 (5.6%) | |
Photopsia | 1/18 (5.6%) | |
Vision blurred | 1/18 (5.6%) | |
Gastrointestinal disorders | ||
Abdominal discomfort | 1/18 (5.6%) | |
Abdominal pain | 2/18 (11.1%) | |
Colitis | 1/18 (5.6%) | |
Constipation | 3/18 (16.7%) | |
Diarrhoea | 8/18 (44.4%) | |
Flatulence | 3/18 (16.7%) | |
Gastrointestinal pain | 1/18 (5.6%) | |
Gastrooesophageal reflux disease | 1/18 (5.6%) | |
Haemorrhoidal haemorrhage | 1/18 (5.6%) | |
Lip discolouration | 1/18 (5.6%) | |
Nausea | 7/18 (38.9%) | |
Oral pain | 1/18 (5.6%) | |
Painful defaecation | 1/18 (5.6%) | |
Paraesthesia oral | 1/18 (5.6%) | |
Vomiting | 5/18 (27.8%) | |
General disorders | ||
Asthenia | 2/18 (11.1%) | |
Chest pain | 1/18 (5.6%) | |
Chills | 2/18 (11.1%) | |
Fatigue | 8/18 (44.4%) | |
Influenza like illness | 2/18 (11.1%) | |
Malaise | 2/18 (11.1%) | |
Pain | 2/18 (11.1%) | |
Pyrexia | 5/18 (27.8%) | |
Hepatobiliary disorders | ||
Hyperbilirubinaemia | 1/18 (5.6%) | |
Infections and infestations | ||
Atypical pneumonia | 1/18 (5.6%) | |
Candida infection | 1/18 (5.6%) | |
Conjunctivitis | 1/18 (5.6%) | |
Hordeolum | 1/18 (5.6%) | |
Nasopharyngitis | 2/18 (11.1%) | |
Upper respiratory tract infection | 4/18 (22.2%) | |
Injury, poisoning and procedural complications | ||
Contusion | 2/18 (11.1%) | |
Fall | 1/18 (5.6%) | |
Investigations | ||
Alanine aminotransferase increased | 8/18 (44.4%) | |
Aspartate aminotransferase increased | 8/18 (44.4%) | |
Blood bilirubin increased | 2/18 (11.1%) | |
Blood creatinine increased | 1/18 (5.6%) | |
Blood phosphorus increased | 1/18 (5.6%) | |
Blood uric acid increased | 1/18 (5.6%) | |
Glomerular filtration rate decreased | 1/18 (5.6%) | |
Hepatic enzyme increased | 1/18 (5.6%) | |
Neutrophil count decreased | 1/18 (5.6%) | |
Transaminases increased | 4/18 (22.2%) | |
Weight decreased | 2/18 (11.1%) | |
Metabolism and nutrition disorders | ||
Decreased appetite | 3/18 (16.7%) | |
Dehydration | 1/18 (5.6%) | |
Hyperuricaemia | 1/18 (5.6%) | |
Hypokalaemia | 1/18 (5.6%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 2/18 (11.1%) | |
Back pain | 2/18 (11.1%) | |
Flank pain | 1/18 (5.6%) | |
Haemarthrosis | 1/18 (5.6%) | |
Joint stiffness | 1/18 (5.6%) | |
Muscle spasms | 2/18 (11.1%) | |
Muscular weakness | 1/18 (5.6%) | |
Musculoskeletal pain | 1/18 (5.6%) | |
Pain in extremity | 3/18 (16.7%) | |
Nervous system disorders | ||
Dysgeusia | 3/18 (16.7%) | |
Headache | 4/18 (22.2%) | |
Hypersomnia | 1/18 (5.6%) | |
Lethargy | 2/18 (11.1%) | |
Mental impairment | 1/18 (5.6%) | |
Neuropathy peripheral | 1/18 (5.6%) | |
Sinus headache | 1/18 (5.6%) | |
Psychiatric disorders | ||
Agitation | 2/18 (11.1%) | |
Confusional state | 1/18 (5.6%) | |
Emotional disorder | 1/18 (5.6%) | |
Insomnia | 5/18 (27.8%) | |
Renal and urinary disorders | ||
Chromaturia | 1/18 (5.6%) | |
Dysuria | 1/18 (5.6%) | |
Nocturia | 1/18 (5.6%) | |
Pollakiuria | 1/18 (5.6%) | |
Renal failure | 1/18 (5.6%) | |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 4/18 (22.2%) | |
Dysphonia | 1/18 (5.6%) | |
Dyspnoea | 2/18 (11.1%) | |
Hypopnoea | 1/18 (5.6%) | |
Nasal congestion | 1/18 (5.6%) | |
Oropharyngeal pain | 1/18 (5.6%) | |
Pneumonitis | 2/18 (11.1%) | |
Productive cough | 1/18 (5.6%) | |
Skin and subcutaneous tissue disorders | ||
Acne | 1/18 (5.6%) | |
Exfoliative rash | 3/18 (16.7%) | |
Hyperhidrosis | 2/18 (11.1%) | |
Hyperkeratosis | 1/18 (5.6%) | |
Pruritus | 3/18 (16.7%) | |
Rash | 5/18 (27.8%) | |
Skin fissures | 1/18 (5.6%) | |
Vascular disorders | ||
Hot flush | 1/18 (5.6%) | |
Hypotension | 1/18 (5.6%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title | Clinical Trial Disclosures |
---|---|
Organization | Gilead Sciences |
Phone | |
ClinicalTrialDisclosures@gilead.com |
- 101-10